Hypervalent silicon complexes generated from Lewis base catalysts and chlorosilanes are very reactive intermediates and continue to be an important source for the development of new chemical methodologies in organic synthesis. The unique reactivity profiles, non-toxicity and ready availability of chlorosilanes have yielded an impressive array of chemical methods and processes. This proposal seeks to innovate the ability of chlorosilanes to deliver carbon nucleophiles under Lewis base catalysis conditions through integrated experimental and computational investigations, and to apply it to novel condensation reactions with readily available non-activated ketones and ketimines. These challenging transformations will be rendered enantioselective through the development of conceptually new classes of chiral Lewis base catalysts. The utility of the resulting methods will be demonstrated by the asymmetric synthesis of pharmaceuticals and biologically relevant molecules. Goals of the research program include advancing Lewis base catalysis of chlorosilanes at the fundamental level, and new reaction development that will provide rapid, efficient access to novel chiral building blocks bearing the oxygen- and nitrogen-substituted quaternary stereocenters. We will focus on the transformations that can provide chiral synthetic intermediates that are either inaccessible or very difficult to obtain with currently available methods. The results are expected to transform the way chlorosilanes are utilized in asymmetric synthesis.